Yuanguo Xiong, Hao Xin, Cai Shi, Xianxi Guo, Ying Chen, Caifei Huang, Fuwang Ma, Ge Yang, Jian Yang
Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Pharmacy, Qingdao Third People's Hospital Affiliated to Qingdao University, Qingdao, China.
Front Pharmacol. 2025 Jun 4;16:1558054. doi: 10.3389/fphar.2025.1558054. eCollection 2025.
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to global health crisis. Although several antiviral drugs have been used to mitigate the severity and mortality of COVID-19, the safety profile remained a critical concern. Azvudine, a new nucleoside analog, has been approved for emergency use in China for COVID-19. However, the incidence and risk factors associated with Azvudine-induced hepatotoxicity in hospitalized patients remained unclear.
To assess the prevalence, risk factors, clinical patterns, and outcomes of Azvudine-induced hepatotoxicity by real-world data.
We conducted a single-center retrospective case-control study at Renmin Hospital of Wuhan University, including patients administered Azvudine for COVID-19 treatment between December 2022 and May 2023. Univariate and multivariate logistic regression analyses were preformed to assess risk factors for Azvudine-associated or -induced hepatotoxicity. Receiver operating characteristic (ROC) curve analysis was performed to calculate the area under the ROC curve (AUC).
In total, 669 patients were included in the Azvudine-associated hepatotoxicity research. 47.1% patients exhibited hepatotoxicity, abnormal liver function on admission [OR: 5.55 (3.94-7.90), 0.001] and antithrombotic drugs [OR: 1.79 (1.27-2.54), 0.001] were independent predictors of Azvudine-associated hepatotoxicity, with the area under the ROC curve (AUC) was 0.756 [95% CI: 0.719-0.792, 0.001]. Further studies of Azvudine-induced hepatotoxicity revealed 294 cases, of which 27.2% showed hepatotoxicity. The concomitant use of antivirals [OR: 3.80 (1.47-10.1), 0.006] and anticoagulant drugs [OR: 3.12 (1.77-5.61), 0.001], particularly Ganciclovir [OR: 4.11 (1.45-12.2), 0.008], Low-Molecular-Weight Heparin Calcium [OR: 3.00 (1.69-5.33), 0.001], and Enoxaparin [OR: 2.68 (0.99-7.10), 0.047], were significantly associated with an increased risk of hepatotoxicity. Most hepatotoxicity cases were mild, and recovered or improved after drug withdrawal and treatment, whereas severe cases contributed to the progression of the primary disease and increased mortality risk.
Our study provided evidence of the significant association between Azvudine and hepatotoxicity in hospitalized COVID-19 patients. These findings underscored the importance of monitoring liver function during Azvudine treatment and caution against concomitant use of certain medications. Further research was warranted to elucidate the mechanisms underlying Azvudine-induced hepatotoxicity and optimize clinical management strategies.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒引起的2019冠状病毒病（COVID-19）大流行已导致全球健康危机。尽管已使用多种抗病毒药物来减轻COVID-19的严重程度和死亡率，但安全性仍然是一个关键问题。阿兹夫定，一种新型核苷类似物，已在中国被批准用于COVID-19的紧急治疗。然而，住院患者中与阿兹夫定诱导的肝毒性相关的发生率和危险因素仍不清楚。
通过真实世界数据评估阿兹夫定诱导的肝毒性的患病率、危险因素、临床模式和结局。
我们在武汉大学人民医院进行了一项单中心回顾性病例对照研究，纳入了2022年12月至2023年5月期间接受阿兹夫定治疗COVID-19的患者。进行单因素和多因素逻辑回归分析以评估与阿兹夫定相关或诱导的肝毒性的危险因素。进行受试者操作特征（ROC）曲线分析以计算ROC曲线下面积（AUC）。
共有669例患者纳入阿兹夫定相关肝毒性研究。47.1%的患者出现肝毒性，入院时肝功能异常[比值比（OR）：5.55（3.94-7.90），P<0.001]和抗血栓药物[OR：1.79（1.27-2.54），P<0.001]是阿兹夫定相关肝毒性的独立预测因素，ROC曲线下面积（AUC）为0.756[95%置信区间（CI）：0.719-0.792，P<0.001]。对阿兹夫定诱导的肝毒性的进一步研究发现294例病例，其中27.2%表现出肝毒性。同时使用抗病毒药物[OR：3.80（1.47-10.1），P=0.006]和抗凝药物[OR：3.12（1.77-5.61），P<0.001]，特别是更昔洛韦[OR：4.11（1.45-1十二点二），P=0.008]、低分子肝素钙[OR：3.00（1.69-5.33），P<0.（001）]和依诺肝素[OR：2.68（0.99-7.10），P=0.047]，与肝毒性风险增加显著相关。大多数肝毒性病例为轻度，停药和治疗后恢复或改善，而严重病例导致原发疾病进展并增加死亡风险。
我们的研究提供了证据表明阿兹夫定与住院COVID-19患者的肝毒性之间存在显著关联。这些发现强调了在阿兹夫定治疗期间监测肝功能以及谨慎使用某些药物的重要性。有必要进行进一步研究以阐明阿兹夫定诱导肝毒性的潜在机制并优化临床管理策略。
